Dataset Information

Metabolic phenotyping of healthy and diseased human RPE cells.

ABSTRACT:

Purpose

Metabolic defects in retinal pigment epithelium (RPE) are underlying many retinal degenerative diseases. This study aims to identify the nutrient requirements of healthy and diseased human RPE cells.

Methods

We profiled the utilization of 183 nutrients in human RPE cells: 1) differentiated and dedifferentiated fetal RPE (fRPE), 2) induced pluripotent stem cell derived-RPE (iPSC RPE), 3) Sorsby fundus dystrophy (SFD) patient-derived iPSC RPE and its CRISPR-corrected isogenic SFD (cSFD) iPSC RPE, and 5) ARPE-19 cell lines cultured under different conditions.

Results

Differentiated fRPE cells and healthy iPSC RPE cells can utilize 51 and 48 nutrients respectively, including sugars, intermediates from glycolysis and tricarboxylic acid (TCA) cycle, fatty acids, ketone bodies, amino acids, and dipeptides. However, when fRPE cells lose epithelial phenotype through dedifferentiated, they can only utilize 17 nutrients, primarily sugar and glutamine-related amino acids. SFD RPE cells can utilize 37 nutrients; however, Compared to cSFD RPE and healthy iPSC RPE, they are unable to utilize lactate, some TCA cycle intermediates, and short-chain fatty acids. Nonetheless, they show increased utilization of branch-chain amino acids (BCAAs) and BCAA-containing dipeptides. The dedifferentiated ARPE-19 cells in traditional culture media cannot utilize lactate and ketone bodies. In contrast, nicotinamide supplementation promotes differentiation into epithelial phenotype, restoring the ability to use these nutrients.

Conclusions

Epithelial phenotype confers metabolic flexibility to the RPE for utilizing various nutrients. SFD RPE cells have reduced metabolic flexibility, relying on the oxidation of BCAAs. Our findings highlight the importance of nutrient availability and utilization in RPE differentiation and diseases.

SUBMITTER: Rizwan S

PROVIDER: S-EPMC10925320 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Metabolic phenotyping of healthy and diseased human RPE cells.

Rizwan Saira S Toothman Beverly B Li Bo B Engel Abbi J AJ Lim Rayne R RR Niernberger Sheldon S Lu Jinyu J Ratliff Cloe C Xiang Yinxiao Y Eminhizer Mark M Chao Jennifer R JR Du Jianhai J

bioRxiv : the preprint server for biology 20240718

<h4>Purpose</h4>Metabolic defects in the retinal pigment epithelium (RPE) underlie many retinal degenerative diseases. This study aims to identify the nutrient requirements of healthy and diseased human RPE cells.<h4>Methods</h4>We profiled nutrient utilization of various human RPE cells, including differentiated and dedifferentiated fetal RPE (fRPE), induced pluripotent stem cell derived-RPE (iPSC RPE), Sorsby fundus dystrophy (SFD) patient-derived iPSC RPE, CRISPR-corrected isogenic SFD (cSFD) ...[more]

PMID: 38464098

Similar Datasets

Project description:This work will use a new approach to measure how surgery effects human biochemistry and metabolism. It will create a metabolic signature or ‘phenotype’ for surgical injury that will help clinicians choose the right surgical treatments for an individual. This is because metabolism is based on an individual’s genes, disease burden and environmental influences such as gut microbiota. This study will use a scientific method based on computational analysis of spectra taken from techniques known as Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR) spectroscopy. This science is called ‘metabonomics’ and it has many advantages. Firstly, it provides a measure of thousands of metabolites at a single moment in time that are unique to the individual and it therefore gives a ‘systems’ overview of a persons metabolism. Secondly it is able to process many hundreds of samples quickly. The investigators are aiming to integrate the investigators metabolic data with genetic information about patients or bacteria wherever possible. This will be the first time that a ‘systems biology’ approach has been used in surgery, with potentially significant gains to me made in pre operative risk stratification and optimisation. By performing this analysis at all stages of the surgical journey (preoperatively, during the operation and after the surgery) it will ensure the right treatments are given to the right patient at the right time. By creating longitudinal models of the biochemical responses to surgery, predict at a much earlier stage those patients at risk of developing complications. This will improve outcome after surgery. This work will use a metabonomic approach to create new tools for surgeons to use during operations based on tissue biology. For example the investigators will be able to measure the metabolic content of tumours in real time by measuring the biological content of diathermy smoke. This has the potential to change intra-operative decision making and further improve outcome.

Dataset Information

Metabolic phenotyping of healthy and diseased human RPE cells.

Purpose

Methods

Results

Conclusions

Publications

Metabolic phenotyping of healthy and diseased human RPE cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets